2024
Maturation of germinal center B cells after influenza virus vaccination in humans
McIntire K, Meng H, Lin T, Kim W, Moore N, Han J, McMahon M, Wang M, Malladi S, Mohammed B, Zhou J, Schmitz A, Hoehn K, Carreño J, Yellin T, Suessen T, Middleton W, Teefey S, Presti R, Krammer F, Turner J, Ward A, Wilson I, Kleinstein S, Ellebedy A. Maturation of germinal center B cells after influenza virus vaccination in humans. Journal Of Experimental Medicine 2024, 221: e20240668. PMID: 38935072, PMCID: PMC11211068, DOI: 10.1084/jem.20240668.Peer-Reviewed Original ResearchConceptsB cellsInfluenza vaccineGerminal centersAntigen-specific GC B cellsResponse to seasonal influenza vaccinationLong-lived bone marrow plasma cellsResponse to influenza vaccinationBone marrow plasma cellsGerminal center B cellsGC B cell clonesInfluenza virus vaccineMaturation of B cellsMarrow plasma cellsSeasonal influenza vaccineMemory B cellsHemagglutinin (HAB cell clonesGC B cellsInfluenza hemagglutinin (HAH5 HANeedle aspirationLymphoid structuresLymph nodesPlasma cellsGC reactionIntegrated longitudinal multiomics study identifies immune programs associated with acute COVID-19 severity and mortality
Gygi J, Maguire C, Patel R, Shinde P, Konstorum A, Shannon C, Xu L, Hoch A, Jayavelu N, Haddad E, Network I, Reed E, Kraft M, McComsey G, Metcalf J, Ozonoff A, Esserman D, Cairns C, Rouphael N, Bosinger S, Kim-Schulze S, Krammer F, Rosen L, van Bakel H, Wilson M, Eckalbar W, Maecker H, Langelier C, Steen H, Altman M, Montgomery R, Levy O, Melamed E, Pulendran B, Diray-Arce J, Smolen K, Fragiadakis G, Becker P, Sekaly R, Ehrlich L, Fourati S, Peters B, Kleinstein S, Guan L. Integrated longitudinal multiomics study identifies immune programs associated with acute COVID-19 severity and mortality. Journal Of Clinical Investigation 2024, 134: e176640. PMID: 38690733, PMCID: PMC11060740, DOI: 10.1172/jci176640.Peer-Reviewed Original ResearchConceptsClinical outcomesImmune cascadeElevated levels of inflammatory cytokinesDisease severityLevels of inflammatory cytokinesFormation of neutrophil extracellular trapsAcute COVID-19 severityCritically ill patientsNeutrophil extracellular trapsDevelopment of therapiesCOVID-19 cohortCOVID-19 severityViral clearanceImmunosuppressive metabolitesDeep immunophenotypingMultiomic modelIFN-stimulated genesImmunophenotypic assessmentB cellsDisease courseEarly upregulationInflammatory cytokinesDisease progressionIFN inhibitorsExtracellular trapsA supervised Bayesian factor model for the identification of multi-omics signatures
Gygi J, Konstorum A, Pawar S, Aron E, Kleinstein S, Guan L. A supervised Bayesian factor model for the identification of multi-omics signatures. Bioinformatics 2024, 40: btae202. PMID: 38603606, PMCID: PMC11078774, DOI: 10.1093/bioinformatics/btae202.Peer-Reviewed Original ResearchConceptsMulti-omics signaturesBayesian factor modelMulti-omics dataMulti-omics integrationSupplementary dataOmics datasetsMulti-omicsProfiling datasetsR packageDiverse assaysImproved biological understandingProfiling assaysSignature discoveryBioinformaticsProfiling studiesBiological understandingDimensionality reductionBiological responsesBiological signaturesCombination of dimensionality reduction
2022
Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study
Ozonoff A, Schaenman J, Jayavelu ND, Milliren CE, Calfee CS, Cairns CB, Kraft M, Baden LR, Shaw AC, Krammer F, van Bakel H, Esserman DA, Liu S, Sesma AF, Simon V, Hafler DA, Montgomery RR, Kleinstein SH, Levy O, Bime C, Haddad EK, Erle DJ, Pulendran B, Nadeau KC, Davis MM, Hough CL, Messer WB, Higuita NIA, Metcalf JP, Atkinson MA, Brakenridge SC, Corry D, Kheradmand F, Ehrlich LIR, Melamed E, McComsey GA, Sekaly R, Diray-Arce J, Peters B, Augustine AD, Reed EF, Altman MC, Becker PM, Rouphael N, Ozonoff A, Schaenman J, Jayavelu N, Milliren C, Calfee C, Cairns C, Kraft M, Baden L, Shaw A, Krammer F, van Bakel H, Esserman D, Liu S, Sesma A, Simon V, Hafler D, Montgomery R, Kleinstein S, Levy O, Bime C, Haddad E, Erle D, Pulendran B, Nadeau K, Davis M, Hough C, Messer W, Higuita N, Metcalf J, Atkinson M, Brakenridge S, Corry D, Kheradmand F, Ehrlich L, Melamed E, McComsey G, Sekaly R, Diray-Arce J, Peters B, Augustine A, Reed E, McEnaney K, Barton B, Lentucci C, Saluvan M, Chang A, Hoch A, Albert M, Shaheen T, Kho A, Thomas S, Chen J, Murphy M, Cooney M, Presnell S, Fragiadakis G, Patel R, Guan L, Gygi J, Pawar S, Brito A, Khalil Z, Maguire C, Fourati S, Overton J, Vita R, Westendorf K, Salehi-Rad R, Leligdowicz A, Matthay M, Singer J, Kangelaris K, Hendrickson C, Krummel M, Langelier C, Woodruff P, Powell D, Kim J, Simmons B, Goonewardene I, Smith C, Martens M, Mosier J, Kimura H, Sherman A, Walsh S, Issa N, Dela Cruz C, Farhadian S, Iwasaki A, Ko A, Chinthrajah S, Ahuja N, Rogers A, Artandi M, Siegel S, Lu Z, Drevets D, Brown B, Anderson M, Guirgis F, Thyagarajan R, Rousseau J, Wylie D, Busch J, Gandhi S, Triplett T, Yendewa G, Giddings O, Anderson E, Mehta A, Sevransky J, Khor B, Rahman A, Stadlbauer D, Dutta J, Xie H, Kim-Schulze S, Gonzalez-Reiche A, van de Guchte A, Farrugia K, Khan Z, Maecker H, Elashoff D, Brook J, Ramires-Sanchez E, Llamas M, Rivera A, Perdomo C, Ward D, Magyar C, Fulcher J, Abe-Jones Y, Asthana S, Beagle A, Bhide S, Carrillo S, Chak S, Fragiadakis G, Ghale R, Gonzalez A, Jauregui A, Jones N, Lea T, Lee D, Lota R, Milush J, Nguyen V, Pierce L, Prasad P, Rao A, Samad B, Shaw C, Sigman A, Sinha P, Ward A, Willmore A, Zhan J, Rashid S, Rodriguez N, Tang K, Altamirano L, Betancourt L, Curiel C, Sutter N, Paz M, Tietje-Ulrich G, Leroux C, Connors J, Bernui M, Kutzler M, Edwards C, Lee E, Lin E, Croen B, Semenza N, Rogowski B, Melnyk N, Woloszczuk K, Cusimano G, Bell M, Furukawa S, McLin R, Marrero P, Sheidy J, Tegos G, Nagle C, Mege N, Ulring K, Seyfert-Margolis V, Conway M, Francisco D, Molzahn A, Erickson H, Wilson C, Schunk R, Sierra B, Hughes T, Smolen K, Desjardins M, van Haren S, Mitre X, Cauley J, Li X, Tong A, Evans B, Montesano C, Licona J, Krauss J, Chang J, Izaguirre N, Chaudhary O, Coppi A, Fournier J, Mohanty S, Muenker M, Nelson A, Raddassi K, Rainone M, Ruff W, Salahuddin S, Schulz W, Vijayakumar P, Wang H, Wunder E, Young H, Zhao Y, Saksena M, Altman D, Kojic E, Srivastava K, Eaker L, Bermúdez-González M, Beach K, Sominsky L, Azad A, Carreño J, Singh G, Raskin A, Tcheou J, Bielak D, Kawabata H, Mulder L, Kleiner G, Lee A, Do Do E, Fernandes A, Manohar M, Hagan T, Blish C, Din H, Roque J, Yang S, Brunton A, Sullivan P, Strnad M, Lyski Z, Coulter F, Booth J, Sinko L, Moldawer L, Borresen B, Roth-Manning B, Song L, Nelson E, Lewis-Smith M, Smith J, Tipan P, Siles N, Bazzi S, Geltman J, Hurley K, Gabriele G, Sieg S, Vaysman T, Bristow L, Hussaini L, Hellmeister K, Samaha H, Cheng A, Spainhour C, Scherer E, Johnson B, Bechnak A, Ciric C, Hewitt L, Carter E, Mcnair N, Panganiban B, Huerta C, Usher J, Ribeiro S, Altman M, Becker P, Rouphael N. Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study. EBioMedicine 2022, 83: 104208. PMID: 35952496, PMCID: PMC9359694, DOI: 10.1016/j.ebiom.2022.104208.Peer-Reviewed Original ResearchConceptsRisk factorsRadiographic findingsFemale sexDisease severityHospitalized COVID-19 patientsSARS-CoV-2 antibodiesSARS-CoV-2 PCRLong COVID-19Presence of infiltratesInvasive mechanical ventilationCharacteristics of patientsOnly female sexViral load levelsClinical laboratory valuesCOVID-19 cohortMultivariable logistic regressionCOVID-19 patientsCoronavirus disease 2019PCR cycle thresholdCOVID-19Baseline creatinineBaseline lymphopeniaMedian ageOverall mortalityProlonged hospitalizationSingle-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19
Unterman A, Sumida TS, Nouri N, Yan X, Zhao AY, Gasque V, Schupp JC, Asashima H, Liu Y, Cosme C, Deng W, Chen M, Raredon MSB, Hoehn KB, Wang G, Wang Z, DeIuliis G, Ravindra NG, Li N, Castaldi C, Wong P, Fournier J, Bermejo S, Sharma L, Casanovas-Massana A, Vogels CBF, Wyllie AL, Grubaugh ND, Melillo A, Meng H, Stein Y, Minasyan M, Mohanty S, Ruff WE, Cohen I, Raddassi K, Niklason L, Ko A, Montgomery R, Farhadian S, Iwasaki A, Shaw A, van Dijk D, Zhao H, Kleinstein S, Hafler D, Kaminski N, Dela Cruz C. Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19. Nature Communications 2022, 13: 440. PMID: 35064122, PMCID: PMC8782894, DOI: 10.1038/s41467-021-27716-4.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAgedAntibodies, Monoclonal, HumanizedCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCells, CulturedCOVID-19COVID-19 Drug TreatmentFemaleGene Expression ProfilingGene Expression RegulationHumansImmunity, InnateMaleReceptors, Antigen, B-CellReceptors, Antigen, T-CellRNA-SeqSARS-CoV-2Single-Cell AnalysisConceptsProgressive COVID-19B cell clonesSingle-cell analysisT cellsImmune responseMulti-omics single-cell analysisCOVID-19Cell clonesAdaptive immune interactionsSevere COVID-19Dynamic immune responsesGene expressionSARS-CoV-2 virusAdaptive immune systemSomatic hypermutation frequenciesCellular effectsProtein markersEffector CD8Immune signaturesProgressive diseaseHypermutation frequencyProgressive courseClassical monocytesClonesImmune interactions
2021
Intranasal priming induces local lung-resident B cell populations that secrete protective mucosal antiviral IgA
Oh JE, Song E, Moriyama M, Wong P, Zhang S, Jiang R, Strohmeier S, Kleinstein SH, Krammer F, Iwasaki A. Intranasal priming induces local lung-resident B cell populations that secrete protective mucosal antiviral IgA. Science Immunology 2021, 6: eabj5129. PMID: 34890255, PMCID: PMC8762609, DOI: 10.1126/sciimmunol.abj5129.Peer-Reviewed Original ResearchConceptsVirus infectionIgA secretionB cellsMucosal surfacesIgA-secreting B cellsIgA-expressing cellsRole of IgARespiratory virus infectionsIgA-secreting cellsLower respiratory tractInfluenza virus infectionEffective immune protectionHeterologous virus infectionMemory B cellsSecretory immunoglobulin AProtein-based vaccinesB cell populationsPredominant Ig isotypeSite of entryIntranasal primingBronchoalveolar spaceProtective immunityVaccine strategiesRespiratory mucosaImmune protectionElevated N-Linked Glycosylation of IgG V Regions in Myasthenia Gravis Disease Subtypes.
Mandel-Brehm C, Fichtner ML, Jiang R, Winton VJ, Vazquez SE, Pham MC, Hoehn KB, Kelleher NL, Nowak RJ, Kleinstein SH, Wilson MR, DeRisi JL, O'Connor KC. Elevated N-Linked Glycosylation of IgG V Regions in Myasthenia Gravis Disease Subtypes. The Journal Of Immunology 2021, 207: 2005-2014. PMID: 34544801, PMCID: PMC8492536, DOI: 10.4049/jimmunol.2100225.Peer-Reviewed Original ResearchConceptsMyasthenia gravisB-cell-mediated autoimmune diseasesBCR repertoireCell-mediated autoimmune diseaseTotal BCR repertoireTotal circulating IgGSubset of patientsB cell repertoireElevated NGene segment usageMG subtypesAutoimmune disordersAutoimmune diseasesHealthy donorsCell repertoireDisease subtypesDistinct subtypesReceptor repertoireAdaptive immune receptor repertoiresV regionsAutoantigen bindingPatientsSegment usageSubtypesImmune receptor repertoiresSingle cell immunophenotyping of the skin lesion erythema migrans Identifies IgM memory B cells
Jiang R, Meng H, Raddassi K, Fleming I, Hoehn KB, Dardick KR, Belperron AA, Montgomery RR, Shalek AK, Hafler DA, Kleinstein SH, Bockenstedt LK. Single cell immunophenotyping of the skin lesion erythema migrans Identifies IgM memory B cells. JCI Insight 2021, 6: e148035. PMID: 34061047, PMCID: PMC8262471, DOI: 10.1172/jci.insight.148035.Peer-Reviewed Original ResearchConceptsMemory B cellsErythema migransB cellsEM lesionsIgM memory B cellsLyme diseaseB-cell receptor sequencingSkin infection siteCell receptor sequencingEarly Lyme diseaseLocal antigen presentationSkin immune responsesB cell populationsSingle-cell immunophenotypingMHC class II genesUninvolved skinImmune cellsSpirochetal infectionAntigen presentationCell immunophenotypingT cellsImmune responseIsotype usageAntibody productionInitial signs
2020
Human germinal centres engage memory and naive B cells after influenza vaccination
Turner JS, Zhou JQ, Han J, Schmitz AJ, Rizk AA, Alsoussi WB, Lei T, Amor M, McIntire KM, Meade P, Strohmeier S, Brent RI, Richey ST, Haile A, Yang YR, Klebert MK, Suessen T, Teefey S, Presti RM, Krammer F, Kleinstein SH, Ward AB, Ellebedy AH. Human germinal centres engage memory and naive B cells after influenza vaccination. Nature 2020, 586: 127-132. PMID: 32866963, PMCID: PMC7566073, DOI: 10.1038/s41586-020-2711-0.Peer-Reviewed Original ResearchConceptsB cell clonesInfluenza vaccinationGerminal center B cellsB cellsGerminal center reactionCell clonesLymph nodesMonoclonal antibodiesPre-existing memory B cellsGerminal center B cell responsesStrain-specific monoclonal antibodiesCenter reactionUltrasound-guided fine-needle aspirationMajor public health threatEarly plasmablast responsesInfluenza virus vaccinationSeasonal influenza vaccinationCross-reactive monoclonal antibodiesB cell responsesMemory B cellsB-cell originFine-needle aspirationNaive B cellsPublic health threatHuman germinal centre